*Fetal [[Rhesus blood group|Rhesus status]]. This was successful in 95.7% of cases, an application which may more selective administration of [[anti-D antibodies]] to those that are at risk.<ref>[http://www.ncbi.nlm.nih.gov/sites/entrez?itool=abstractplus&db=pubmed&cmd=Retrieve&dopt=abstractplus&list_uids=18390496 Finning K, Martin P, Summers J, Massey E, Poole G, Daniels G. Effect of high throughput RHD typing of fetal DNA in maternal plasma on use of anti-RhD immunoglobulin in RhD negative pregnant women: prospective feasibility study. BMJ (Clinical research ed.). 2008 Apr 3.]<small>(Epub ahead of print) </small><small>([http://dx.doi.org/10.1136/bmj.39518.463206.25 Link to article] &ndash; subscription may be required.)</small></ref>

*Fetal [[Rhesus blood group|Rhesus status]]. This was successful in 95.7% of cases, an application which may more selective administration of [[anti-D antibodies]] to those that are at risk.<ref>[http://www.ncbi.nlm.nih.gov/sites/entrez?itool=abstractplus&db=pubmed&cmd=Retrieve&dopt=abstractplus&list_uids=18390496 Finning K, Martin P, Summers J, Massey E, Poole G, Daniels G. Effect of high throughput RHD typing of fetal DNA in maternal plasma on use of anti-RhD immunoglobulin in RhD negative pregnant women: prospective feasibility study. BMJ (Clinical research ed.). 2008 Apr 3.]<small>(Epub ahead of print) </small><small>([http://dx.doi.org/10.1136/bmj.39518.463206.25 Link to article] &ndash; subscription may be required.)</small></ref>

Free, extra-cellular nucleic acid (CNAPS) can found circulating in the plasma or serum. The nucleic acid in question can be RNA, mitochondrial DNA or genomic DNA, but DNA is generally used as it is less labile than RNA.

While only small levels are detectable in health, higher levels are observed in disease, for instance malignancy and SLE. In malignancy, mutations from the tumour can be detected in this pool of nucleic acid. Similarly, fetal DNA can be detected in small amounts in maternal circulation.[1] CNAPS represents a phenomenon which may be exploited for diagnosis.

Contents

Historical Aspects

The phenomenon of extra-cellular DNA was first described in 1948 even prior to the publication of Watson and Crick's landmark paper on the structure of DNA.[2] The implications of the 1948 study lay unexplored until interest was rekindled by the discovery of free DNA in systemic lupus erythematosus.[3] Investigation of other diseases revealed increased levels in inflammatory states, other auto-immune disorders and cancer. High levels of free DNA were seen in a variety of cancers, particularly in patients with metastatic disease,[4][5][6] where higher levels generally carries a poorer prognosis.

The circulating DNA present in health is thought to derive from nucleated blood cells.[7][8] Evidence to support tumour cells as the source of this DNA was initially based on biophysical differences between wildtype DNA and apparent tumour DNA.[9] More convincing proof came from the detection of tumour-specific mutations in circulating DNA that matched mutations in the cancer cells, specifically mutated N-ras in patients with myelodysplasia and acute myeloid leukaemia,[10] and defective K-ras pancreatic cancers.[11] Since then, accumulating qualitative and quantitative evidence has demonstrated not only that circulating DNA is increased in individuals with malignancy, but that the same genetic and epigenetic alterations detected in free DNA can also be identified in the tumour cells.

CNAPS in Malignancy

Exact mechanism of release unclear. Could be due to necrosis of malignant tumour cells, apoptosis, phagocytosis of apoptotic cells, or decreased cleareance.

CNAPS in Pregnancy

Fetal DNA crosses the placenta and can be found in the maternal circulation.

In the research context, this DNA has been used experimentally in prenatal diagnosis of: